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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

28卷

期数:

2022年05期

页码:

508

栏目:

基础医学

出版日期:

2022-09-20

文章信息/Info

Title:

Mechanical loading treats osteoarthritis by promoting the migration and chondrogenic differentiation of infrapatellar fat pad stem cells

文章编号:

1006-8147(2022)05-0508-06

作者:

王筱郁¹; 李杰¹; 2; 李心乐¹; 2; 刘大全¹; 2; 张平¹; 2; 3

（1.天津医科大学基础医学院人体解剖与组织胚胎学系，天津 300070；2.卫生部激素与发育重点实验室，天津市代谢性疾病重点实验室，天津 300134；3.天津市脊柱脊髓重点实验室，天津300052）

Author(s):

WANG Xiao-yu¹; LI Jie¹; 2; LI Xin-le¹; 2; LIU Da-quan¹; 2; ZHANG Ping¹; 2; 3

（1. Department of Anatomy and Histology，School of Basic Medical Sciences，Tianjin Medical University，Tianjin 300070，China; 2. Key Laboratory of Hormones and Development（Ministry of Health），Tianjin Key Laboratory of Metabolic Diseases，Tianjin 300134，China；3. Tianjin Key Laboratory of Spine and Spinal Cord，Tianjin 300052，China）

关键词:

机械加载; 骨关节炎; 髌下脂肪垫干细胞; 迁移; 软骨分化

Keywords:

mechanical loading; osteoarthritis; infrapatellar fat pad stem cells; migration; chondrogenic differentiation

分类号:

R684.3

DOI:

-

文献标志码:

A

摘要:

目的：探究机械加载对骨关节炎小鼠髌下脂肪垫干细胞（IFP-SCs）的动员作用。方法：54只雌性C57BL/6小鼠通过随机数字表法分为对照组（Sham组，n=18）、骨关节炎组（OA组，n=18）、骨关节炎机械加载组（OAL组，n=18）。采用DMM手术建立OA模型，OAL组进行2周的机械加载治疗（条件为1 N，5 Hz，6 min/d）。HE和番红O染色评估小鼠OA模型的软骨损伤程度。免疫荧光、细胞迁移实验、Western印迹等方法检测干细胞的迁移和软骨形成能力。结果：机械加载降低了OA小鼠的国际骨关节炎研究学会（OARSI）评分（t=4.025，P<0.01）。与OA组相比，OAL组IFP-SCS的迁移能力增加（t=-5.142，P<0.001），同时软骨中基质细胞衍生因子（SDF-1）和IFP-SCs中C-X-C趋化因子受体4（CXCR4）的表达增加（t=-4.403，P<0.01）。此外，机械加载使软骨分化中重要的转录因子SRY相关高迁移率族盒蛋白9（SOX9）上调，促进了IFP-SCs软骨分化（t=-11.170，P<0.01）。结论：机械加载通过促进IFP-SCs迁移和软骨分化，促进骨关节炎小鼠软骨修复。

Abstract:

Objective：To explore the effect of mechanical loading on the mobilization of infrapatellar fat pad stem cells（IFP-SCs） in osteoarthritis mice. Methods: Fifty-four female C57BL/6 mice were divided into three groups by random number table method: the sham control group （Sham，n=18），the osteoarthritis group（OA，n=18），and the osteoarthritis with mechanical loading group（OAL group，n=18）. The OA model was established by DMM surgery. The OAL group received loading treatment for 2 weeks（the conditions are 1 N，5 Hz，6 min/d）. The degree of cartilage damage in a mouse model of osteoarthritis was evaluated with HE and Safranin O staining. Immunofluorescence，cell migration assay，and Western blotting analysis were used to evaluate the migration and chondrogenic formation ability of stem cells. Results: Mechanical loading reduced the OARSI（Osteoarthritis Research Society International） score of OA mice（t=4.025，P<0.01).Compared with the OA group，the migration of IFP-SCs was enhanced（t=-5.142，P<0.001），and the expression of stromal cell derived factor-1（SDF-1） in cartilage and C-X-C motif chemokine receptor 4（CXCR4） in infrapatellar fat pad stem cells（IFP-SCs）were increased（t=-4.403，P<0.01）. In addition，mechanical loading promoted IFP-SCs chondrogenic differentiation via up-regulation of SRY-related high mobility group-box 9（SOX9） which was an important transcription factor in chondrogenic differentiation（t=-11.170，P<0.01）. Conclusion: Mechanical loading facilitates cartilage repair in osteoarthritis mice by promoting the migration and chondrogenic differentiation of infrapatellar fat pad stem cells.

参考文献/References:

[1] GLYN-JONES S，PALMER A J，AGRICOLA R，et al. Osteoarthritis[J]，Lancet，2015，386（9991）：376-387.
[2] HUNTER D J，BIERMA-ZEINSTRA S. Osteoarthritis[J]，Lancet，2019，393（10182）：1745-1759.
[3] STEWART M，CIBERE J，SAYRE E C，et al. Efficacy of commonly prescribed analgesics in the management of osteoarthritis： a systematic review and meta-analysis[J]. Rheumatol Int，2018，38（11）：1985-1997.
[4] ZHANG S，HU B，LIU W，et al. Articular cartilage regeneration： the role of endogenous mesenchymal stem/progenitor cell recruitment and migration[J]. Semin Arthritis Rheum，2020，50（2）：198-208.
[5] YANG Z，LI H，YUAN Z，et al. Endogenous cell recruitment strategy for articular cartilage regeneration[J].Acta Biomater，2020，114：31-52.
[6] MCGONAGLE D，BABOOLAL T G，JONES E. Native joint-resident mesenchymal stem cells for cartilage repair in osteoarthritis[J]. Nat Rev Rheumatol，2017，13（12）：719-730.
[7] VAHEDI P，MOGHADDAMSHAHABI R，WEBSTER T J，et al. The use of infrapatellar fat pad-derived mesenchymal stem cells in articular cartilage regeneration：a review[J]. Int J Mol Sci，2021，22（17）：9215.
[8] 陈墅，周义钦，周嵘，等.髌下脂肪垫来源的的间充质干细胞软骨分化的研究进展[J]. 中华关节外科杂志（电子版），2018，12（3）：379-384.
[9] DO AMARAL RJFC，ALMEIDA H V，KELLY D J，et al. Infrapatellar fat pad stem cells：from developmental biology to cell therapy[J].Stem Cells Int，2017，2017：6843727.
[10] DE BARI C，ROELOFS A J. Stem cell-based therapeutic strategies for cartilage defects and osteoarthritis[J]. Curr Opin Pharmacol，2018，40：74-80.
[11] 于咏，李心乐，刘大全，等.机械加载减轻骨关节炎小鼠的病理进展[J].天津医药，2019，47（5）：479-483，564.
[12] ZHENG W，LI X，LIU D，et al. Mechanical loading mitigates osteoarthritis symptoms by regulating endoplasmic reticulum stress and autophagy[J]. FASEB J，2019，33（3）：4077-4088.
[13] WANG X，LI X，LI J，et al. Mechanical loading stimulates bone angiogenesis through enhancing type H vessel formation and downregulating exosomal miR-214-3p from bone marrow-derived mesenchymal stem cells[J]. FASEB J，2021，35（1）：e21150.
[14] LIU D，LI X，LI J，et al. Knee loading protects against osteonecrosis of the femoral head by enhancing vessel remodeling and bone healing[J]. Bone，2015，81：620-631.
[15] LI X，YANG J，LIU D，et al. Knee loading inhibits osteoclast lineage in a mouse model of osteoarthritis[J].Sci Rep，2016，6：24668.
[16] ARMIENTO A R，STODDART M J，ALINI M，et al. Biomaterials for articular cartilage tissue engineering： learning from biology[J]. Acta Biomater，2018，65：1-20.
[17] LI X，LIU D，LI J，et al. Wnt3a involved in the mechanical loading on improvement of bone remodeling and angiogenesis in a postmenopausal osteoporosis mouse model[J]. FASEB J，2019，33（8）：8913-8924.
[18] ABDURAHMAN A，LI X，LI J，et al. Loading-driven PI3K/Akt signaling and erythropoiesis enhanced angiogenesis and osteogenesis in a postmenopausal osteoporosis mouse model[J]. Bone，2022，157：116346.
[19] ZHENG W，DING B，LI X，et al. Knee loading repairs osteoporotic osteoarthritis by relieving abnormal remodeling of subchondral bone via Wnt/β-catenin signaling[J]. FASEB J，2020，34（2）：3399-3412.
[20] ZHENG W，LI X，LI J，et al. Mechanical loading mitigates osteoarthritis symptoms by regulating the inflammatory microenvironment in a mouse model[J]. Ann N Y Acad Sci，2022，online ahead of print.
[21] SHANG F，YU Y，LIU S，et al. Advancing application of mesenchymal stem cell-based bone tissue regeneration[J]. Bioact Mater，2020，6（3）：666-683.
[22] XIANG X，LIU H，WANG L，et al. Ultrasound combined with SDF-1α chemotactic microbubbles promotes stem cell homing in an osteoarthritis model[J]. J Cell Mol Med，2020，24（18）：10816-10829.
[23] XIA P，WANG X，WANG Q，et al. Low-intensity pulsed ultrasound promotes autophagy-mediated migration of mesenchymal stem cells and cartilage repair[J]. Cell Transplant，2021，30：963689720986142.
[24] YUAN L，SAKAMOTO N，SONG G，et al. Low-level shear stress induces human mesenchymal stem cell migration through the SDF-1/CXCR4 axis via MAPK signaling pathways[J]. Stem Cells Dev，2013，22（17）：2384-2393.
[25] 杨爽，闫景龙. 软骨细胞分化过程中SOX9的作用[J]. 中国组织工程研究，2021，26（14）：2279-2284.
[26] ALMALKI S G，AGRAWAL D K. Key transcription factors in the differentiation of mesenchymal stem cells[J]. Differentiation，2016，92（1/2）：41-51.
[27] ZHANG X，WU S，ZHU Y，et al. Exploiting joint-resident stem cells by exogenous SOX9 for cartilage regeneration for therapy of osteoarthritis[J]. Front Med（Lausanne），2021，8：622609.
[28] LUO L，THORPE S D，BUCKLEY C T，et al. The effects of dynamic compression on the development of cartilage grafts engineered using bone marrow and infrapatellar fat pad derived stem cells[J]. Biomed Mater，2015，10（5）：55011.

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备注/Memo

备注/Memo:

基金项目 天津市教委科研计划项目（2019KJ169）
作者简介 王筱郁（1995-），女，硕士在读，研究方向：机械加载治疗骨关节炎的机制研究；通信作者：张平，E-mail：pizhang@tmu.edu.cn。

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更新日期/Last Update: 2022-09-20